Background: Since the introduction of the SLICC criteria in 2012, biopsy-proven lupus nephritis (LN) has been the only independent diagnostic criterion for systemic lupus erythematosus (SLE). This was reaffirmed by the EULAR/ACR in 2019, emphasizing the importance of renal biopsy in LN. However, the current classification lacks specific histopathological criteria for defining LN. This study describes the histological findings of patients with LN, compares them with those of other glomerular diseases, and evaluates their diagnostic accuracy. Methods: This retrospective cohort included 731 kidney biopsies. The patients were divided into two groups: a LN group and a control group comprising patients with membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, pauci-immune glomerulonephritis, and proliferative glomerulonephritis. Sensitivity and specificity analyses were conducted for various histopathological features. Results: We identified five features strongly correlated with LN: mesangial proliferation, subendothelial deposits, C1q staining ≥ 1+, dominant IgG, and ≥ 4 positive immunofluorescence elements. Combined, these features yielded an area under the ROC curve of 0.94 (95% CI: 0.91–0.95). In membranous nephropathy, histological features such as mesangial deposits, C1q positivity, and ≥ 4 positive immunofluorescence elements effectively distinguished class V LN from non-lupus membranous nephropathy, with an area under the ROC curve of 0.85 (95% CI: 0.76–0.93). Conclusion: The combination of mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥ 4 positive immunofluorescence elements offer good accuracy for diagnosing renal involvement in SLE. In the absence of pathognomonic features, combined criteria are valuable diagnostic tools, particularly when other SLE criteria are lacking.